Proximal esophageal impedance baseline increases the yield of impedance-pH and is associated with response to PPIs in chronic cough patients.

BACKGROUND: Chronic cough significantly impairs the quality of life. Although various studies focused on MNBI as assessed in the distal esophagus, scarce data are available on the clinical value of proximal measurements. AIM: To investigate the role of proximal MNBI in the workup of patients with chronic cough and its ability to predict PPI response. METHODS: Demographic, clinical, endoscopy findings, impedance-pH and HRM tracings from consecutive cough patients were evaluated. MNBI was calculated at proximal and distal esophagus. RESULTS: One hundred and sixty four patients were included. In addition to traditional variables, when considering also the PSPW index or MNBI at 3 cm or 15 cm, the proportion of patients with pathological impedance-pH monitoring significantly increased. 70/164 patients were responders, while 94 (57.3%) were non-responder to double PPI dose (p < 0.05). Patients with pathologic MNBI at 3 cm and/or 15 cm as well as those with pathologic PSPW index were characterized by a significantly higher proportion of responders than that observed among patients with normal impedance-pH variables (p < 0.001). The proportion of responders with pathological MNBI at 15 cm was significantly higher than the proportion of responders with pathological MNBI at 3 cm (82.8% vs. 64.3%, p < 0.05). At multivariable model, pathological MNBI at both 3 cm and 15 cm as well as PSPW index were associated with PPI responsiveness. The strongest association with PPI response was observed for MNBI at 15 cm. CONCLUSIONS: The assessment of MNBI at proximal esophagus increases the diagnostic yield of impedance-pH monitoring and may represent a useful predictor of PPI responsiveness in the cumbersome clinical setting of suspected reflux-related cough.

Chicago Classification v4.0 Stratifies Acid Burden and Abnormal Impedance-pH Variables Better Than Chicago Classification v3.0 Chicago Classification v4.0 and GERD.

INTRODUCTION: Gastroesophageal reflux disease (GERD) severity increases with esophageal body hypomotility, but the impact of Chicago Classification (CC) v4.0 criteria on GERD diagnosis is incompletely understood. METHODS: In patients with GERD evaluated with high-resolution manometry and pH-impedance monitoring, CCv3.0 and CCv4.0 diagnoses were compared. RESULTS: In 247 patients, hypomotility diagnosis decreased from 45.3% (CCv3.0) to 30.0% (CCv4.0, P < 0.001). In contrast, within patients with ineffective esophageal motility, proportions with pathological acid exposure increased from 38% (CCv3.0) to 88% (CCv4.0); baseline impedance and esophageal clearance demonstrated similar findings ( P < 0.05 for each comparison). DISCUSSION: CCv4.0 hypomotility criteria are more specific in supporting GERD evidence compared with CCv3.0.

Wall Thickness Ratio-A New Magnetic Resonance Parameter-Is Associated With the Outcome of Biological Therapy in Patients With Ileal and Ileocolonic Crohn's Disease.

GOALS: The present study was aimed at identifying a new magnetic resonance enterography (MRE) parameter assessing the clinical outcome of biological therapy in patients with active ileal/ileocolonic Crohn's disease (CD). BACKGROUND: Transmural healing (TH) has been associated with improved outcomes in CD. However, some patients with clinical remission and inactive disease at endoscopy do not achieve TH. MATERIALS AND METHODS: Ileal/ileocolonic CD patients scheduled for biological therapy were prospectively evaluated, at baseline (T0) and after 1 year of treatment (T1), with Harvey Bradshaw Index score, blood tests, ileocolonscopy, and MRE. Clinical activity was assessed after 2 years of treatment (T2). Wall thickness ratio (WTR) was calculated in the same affected ileal segment, as the ratio between the ileum wall thickness value at T1 and the ileum wall thickness value at T0. RESULTS: A total of 103 patients were included. Mean WTR at T1 in nonresponders was significantly higher than in responders. At receiver operating characteristic analysis, WTR values were significantly associated to biological therapy responsiveness. A WTR cutoff value of 0.77 mm was identified to discriminate responders from nonresponders (sensitivity: 79%; specificity: 67%). In responders, the proportion of patients with a WTR<0.77 was significantly higher than the proportion of patients achieving TH at T1. Among patients achieving endoscopic remission, 11/29 (37.9%) presented TH, while 20/29 (68.9%) presented WTR<0.77 ( P : 0.035). At multivariate logistic regression analysis, WTR<0.77 was significantly associated to biological therapy response. CONCLUSION: WTR index represents an easy-to-calculate MRE parameter and seems to be a promising tool for monitoring therapeutic response in CD patients during biological therapy.

Review Article title: Natural Compounds with Antimicrobial Activities in oral Candida infections during head and neck radiotherapy.

BACKGROUNDS: Oral colonization and infections are frequently observed in patients during and soon after radiation therapy (RT). Infective mucositis is a common side effect associated with cancer therapy, characterized by an inflammation of the oral mucous membranes with histological mucosal and submucosal changes. Ulcerative mucositis is responsible for significant pain, impairing the patient's nutritional intake and leading to local or systemic infections promoting mycosis due to several species of the genus Candida. According to international guidelines, treatment of candidiasis depends on the infection site and patient's condition. SUMMARY: Recently several studies have shown the protective role of natural compounds counteracting the activity of Candida biofilms. The aim of this review is to discuss the antimicrobial activities of natural compounds in fungal infections, especially Candida spp., during and soon after radiotherapy. Indeed new molecules are being discovered and assessed for their capacity to control Candida spp. growth and, probably in the future, will be used to treat oral candidiasis, overall, during radiotherapy. This review reports several preliminary data about preclinical and clinical evidence of their efficacy in the prevention and/or treatment of mucositis due to Radiotherapy with a brief description of the natural compounds with anti-Candida activities. KEY MESSAGES: The increase in the resistance to the available antifungal drugs related to Candida spp. infections increased as well as drug interactions, urging the development of innovative and more effective agents with antifungal action. Recent preclinical and clinical studies are identifying natural substances with anti-inflammatory and antifungal activity that could be tested in the prevention of candidiasis in patients undergoing radiotherapy. Further studies are needed to confirm these preliminary data.

Poliprotect vs Omeprazole in the Relief of Heartburn, Epigastric Pain, and Burning in Patients Without Erosive Esophagitis and Gastroduodenal Lesions: A Randomized, Controlled Trial.

INTRODUCTION: In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure. METHODS: In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed. RESULTS: A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm. DISCUSSION: Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).

Proximal esophageal impedance baseline increases the yield of impedance-pH monitoring for GERD diagnosis and is associated with heartburn response to PPI.

BACKGROUND: Impairment of esophageal mucosal integrity as assessed by low mean nocturnal baseline impedance (MNBI) measured in the distal esophagus increases the diagnostic yield of impedance-pH in patients with inconclusive GERD diagnosis as defined by Lyon criteria. AIM: To assess the diagnostic yield of MNBI measurement in the proximal esophagus, and its relationship with PPI response. METHODS: Expert review of off-therapy impedance-pH tracings from consecutive patients with heartburn, 80 responders and 80 non-responders to label-dose PPI. Data were compared to those from 36 healthy controls using ROC analysis. Multivariate analysis was performed to measure the strength of association of MNBI with PPI response. RESULTS: A threshold value of 2665 Ω was defined for proximal MNBI by ROC analysis, affording 91.7% sensitivity and 86.5% specificity. Proximal and distal MNBI were significantly lower in non-responder cases as compared to responders. Adding proximal MNBI positivity to pathologic (>6%) acid exposure time (AET) and positive symptom-reflux association, the proportion of patients with abnormal impedance-pH findings increased from 74/160 (46%) to 106/160 (66.3%) (p = 0.0016). Among the 12 patients with pathologic proximal MNBI as the only positive impedance-pH finding, 9 cases (75%) were PPI responders. According to multivariate analysis, AET and pathological distal and proximal MNBI were significantly associated with PPI response, the strongest association observed for proximal MNBI. CONCLUSIONS: Impedance baseline assessment in the proximal esophagus may increase the diagnostic yield of impedance-pH monitoring. Heartburn response to PPI is directly related to ultrastructural mucosal damage in the distal and in the proximal esophagus as well.

Psychological distress in inflammatory bowel disease.

INTRODUCTION: Mental health disorders are common in inflammatory bowel disease (IBD) and affect patients' quality of life, impacting on disease outcomes and health care-related costs. AREAS COVERED: Even if psychological issues in IBD patients are highly burdened in terms of quality of life, psychiatric comorbidities still receive less attention into routine care than the physical symptoms of the disease. The present review provides an overview of recent literature, focusing on the association between perceived stress and IBD outcomes. For this purpose, the epidemiology of more common psychological comorbidities in IBD and their potential effect on the onset and disease course have been examined. Moreover, therapeutic interventions in the management of these patients have also been evaluated. EXPERT OPINION: Screening of patients at high risk of psychological issues is currently an unmet, clinical need in the management of IBD. Under-diagnosed and under-treated mental health disorders in IBD patients may impact outcomes, leading to increased disability and health-care utilization and associated costs. A patient-tailored, integrated model of care in the management of IBD is required to optimize disease outcomes and improve patients' quality of life.

Constipation-Predominant Irritable Bowel Syndrome (IBS-C): Effects of Different Nutritional Patterns on Intestinal Dysbiosis and Symptoms.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by abdominal pain associated with defecation or a change in bowel habits. The pathogenesis of IBS is not completely clear, but it is known to be multifactorial and complex. Endogenous and exogenous factors such as abnormal GI motility, low-grade inflammation, increased epithelial permeability and visceral hypersensitivity, but diet and psychosocial aspects are also recognized as important actors. Furthermore, the interaction between diet and gut microbiota has gained interest as a potential contributor to the pathophysiology of IBS. To date, there is no specific diet for IBS with constipation (IBS-C); however, many studies show that fiber intake, especially soluble fiber such as inulin, could have a positive effect on symptoms. This review aims to evaluate the effects of some nutritional components such as fibers but also functional foods, prebiotics, probiotics and symbiotics on symptoms and microbiota in IBS-C subjects.

Anxiety correlates with excessive air swallowing and PPI refractoriness in patients with concomitant symptoms of GERD and functional dyspepsia.

BACKGROUND: Anxiety may exacerbate GERD and FD symptoms perception and reduce quality of life. As many as 50% of patients with GERD symptoms have incomplete relief with PPI therapy, and psychological factors may influence PPI responsiveness. AIM: The potential relationship between anxiety, excessive air swallowing, and PPI responsiveness was evaluated. METHODS: GERD patients with concomitant FD were prospectively evaluated. Validated structured questionnaires were used to evaluate anxiety, GERD, and FD symptoms. All patients were treated, within the previous year, with at least 8 weeks of standard dose PPI therapy. RESULTS: One hundred sixty-one patients were included. Frequency of non-responders in patients with moderate/severe anxiety was significantly higher compared to patients with mild anxiety (62.7% vs. 37.3%, p < 0.01). Patients with moderate/severe anxiety displayed a significantly higher mean FD symptoms score value compared to patients with mild anxiety. A significantly higher mean number of air swallows were observed in patients with moderate/severe anxiety. At ROC analysis, air swallows and mixed reflux episodes were significantly associated with the presence of PPI refractoriness (AUC: 0.725, 95% CI: 0.645-0.805 and 0.768, 0.692-0.843). According to univariate analysis, an abnormal number of air swallows, mixed reflux episodes and presence of moderate/severe anxiety was significantly associated with PPI refractoriness. CONCLUSION: Our results, if confirmed in in a larger, prospective clinical and therapeutic study, demonstrate the usefulness of an up-front evaluation with anxiety questionnaire and esophageal testing in patients with a broad spectrum of upper gastrointestinal symptoms who fail to respond to PPI treatment, supporting the option of alternative treatment modalities.

Phylogenetic analysis of Prevotella copri from fecal and mucosal microbiota of IBS and IBD patients.

Background: Prevotella copri is the most abundant member of the genus Prevotella that inhabits the human large intestines. Evidences correlated the increase in Prevotella abundance to inflammatory disorders, suggesting a pathobiont role. Objectives: The aim of this study was to investigate the phylogenetic dynamics of P. copri in patients with irritable bowel syndrome (IBS), inflammatory bowel diseases (IBDs) and in healthy volunteers (CTRL). Design: A phylogenetic approach was used to characterize 64 P. copri 16S rRNA sequences, selected from a metagenomic database of fecal and mucosal samples from 52 patients affected by IBD, 44 by IBS and 59 healthy. Methods: Phylogenetic reconstructions were carried out using the maximum likelihood (ML) and Bayesian methods. Results: Maximum likelihood phylogenetic tree applied onto reference and data sets, assigned all the reads to P. copri clade, in agreement with the taxonomic classification previously obtained. The longer mean genetic distances were observed for both the couples IBD and CTRL and IBD and IBS, respect to the distance between IBS and CTRL, for fecal samples. The intra-group mean genetic distance increased going from IBS to CTRLs to IBD, indicating elevated genetic variability within IBD of P. copri sequences. None clustering based on the tissue inflammation or on the disease status was evidenced, leading to infer that the variability seemed to not be influenced by concomitant diseases, disease phenotypes or tissue inflammation. Moreover, patients with IBS appeared colonized by different strains of P. copri. In IBS, a correlation between isolates and disease grading was observed. Conclusion: The characterization of P. copri phylogeny is relevant to better understand the interactions between microbiota and pathophysiology of IBD and IBS, especially for future development of therapies based on microbes (e.g. probiotics and synbiotics), to restore the microbiota in these bowel diseases.

Achalasia, from diagnosis to treatment.

INTRODUCTION: Achalasia is an uncommon esophageal motility disorder and is characterized by alterations of the motility of the esophageal body in conjunction with altered lower esophageal sphincter (LES) relaxation. The clinical presentation of patients with achalasia may be complex; however, the most frequent symptom is dysphagia. The management of patients with achalasia is often challenging, due to the heterogeneous clinical presentation. AREAS COVERED: The diagnosis and management of achalasia has significantly improved in the last years due to the growing availability of high-resolution manometry (HRM) and the implementation in the therapeutic armamentarium of new therapeutic endoscopic procedures. Traditional therapeutic strategies include botulinum toxin injected to the LES and pneumatic balloon dilation. On the other hand, surgical treatments contemplate laparoscopic Heller myotomy and, less frequently, esophagectomy. Furthermore, in the last few years, per oral endoscopic myotomy (POEM) has been proposed as the main endoscopic therapeutic alternative to the laparoscopic Heller myotomy. EXPERT OPINION: Diagnosis and treatment of achalasia still represent a challenging area. However, we believe that an accurate up-front evaluation is, nowadays, necessary in addressing patients with achalasia for a more accurate diagnosis as well as for the best treatment options.

Prospective validation of reflux monitoring by impedance-pH in predicting PPI response in typical GERD.

BACKGROUND: The Lyon Consensus proposed a hierarchical approach to GERD diagnosis based on conventional and new impedance-pH metrics, namely acid exposure time (AET), number of reflux episodes, post-reflux swallow-induced peristaltic wave (PSPW) index, and mean nocturnal baseline impedance (MNBI). AIMS: To define the value of conventional and new impedance-pH parameters as predictors of response to label-dose PPI in typical GERD. METHODS: Consecutive adult patients with typical esophageal symptoms were prospectively studied with impedance-pH monitoring and treated with 8-week label-dose PPI. At the end of the PPI course, symptoms response was assessed. RESULTS: Among 255 patients who entered the study, 168 (65.9%) reported symptom remission. At ROC analysis, both MNBI and PSPW index were significantly associated to PPI responsiveness with AUC of 0.783 and 0.801, respectively. Cut-off values of 1747Ω for MNBI and 50% for PSPW index were identified as discriminators between response and non-response to label-dose PPI. At multivariate analysis, MNBI, PSPW index, and AET >6% were efficient predictors of PPI responses (OR 3, 5.4 and 2.3, respectively). Number of reflux episodes did not predict PPI response. CONCLUSIONS: The novel MII-pH variables together with pathological are highly predictive of response of the typical GERD syndrome to label-dose PPI.

Association between post-reflux swallow-induced peristaltic wave index and esophageal mucosal integrity in patients with GERD symptoms.

BACKGROUND: Impedance-pH monitoring allows evaluation of esophageal chemical clearance, a response to reflux elicited by the esophago-salivary reflex, by means of the post-reflux swallow-induced peristaltic wave (PSPW) index; mucosal integrity can be evaluated by means of mean nocturnal baseline impedance (MNBI) and is regarded as a GERD marker. Currently, the relationship between PSPW index and MNBI has not yet been fully investigated and represents the aim of the present study. METHODS: Impedance-pH tracings from consecutive patients were reviewed. ROC analysis and multivariate regression models were generated to evaluate the association between acid exposure time (AET), total refluxes (TRs), PSPW index, and MNBI. Patients were classified by means of AET thresholds and symptom-reflux association indexes into conclusive and inconclusive GERD, reflux hypersensitivity (RH), and functional heartburn (FH). Pathologic MNBI <2292 Ω was defined according to published outcome studies. KEY RESULTS: Two hundred and thirty patients constituted the study cohort. Overall, a significant direct correlation was observed between PSPW index and MNBI (0.759, p < 0.001). At ROC analysis, a PSPW index cut-off value of 53% was the best discriminator between normal from pathologic MNBI values (sensitivity 88%, specificity 86.4%). Considering AET cut-off of 4% or 6%, a sensitivity of 80.7% and 46% and a specificity of 62.5% and 93.2% were found, respectively. According to multivariate analysis, AET >4% and PSPW index value <53% or <61% were significantly associated with pathologic MNBI values. CONCLUSIONS AND INFERENCES: Esophageal chemical clearance is a major defense mechanism against reflux and its impairment represents a major determinant of reflux-associated mucosal damage.

Relevance of Excessive Air Swallowing in GERD Patients With Concomitant Functional Dyspepsia and Poor Response to PPI Therapy.

GOALS: The present study was aimed at evaluating the possible role of air swallowing in the association between gastroesophageal reflux disease (GERD) symptoms and concomitant functional dyspepsia (FD) and their role in GERD symptom persistence despite proton pump inhibitor (PPI) therapy. BACKGROUND: It has been shown that individuals with excessive air swallowing experience FD. It has been also demonstrated that a consistent group of GERD patients not responding to PPI therapy swallow more air during mealtime and also have more mixed refluxes. MATERIALS AND METHODS: Multichannel intraluminal impedance-pH tracings from consecutive patients were retrospectively evaluated. A validated structured questionnaire was used to evaluate GERD and concomitant FD symptoms. All patients were treated, within the previous year, with at least 8 weeks of standard-dose PPI therapy. RESULTS: A total of 35 patients with conclusive GERD, 35 patients with reflux hypersensitivity, and 35 with functional heartburn were studied. A direct relationship was observed between the number of air swallows and of mixed refluxes ( R =0.64). At receiver operating characteristic curve analysis, air swallows and mixed refluxes were significantly associated to the presence of FD and PPI refractoriness. An air swallow cutoff of 107 episodes/24 hours was identified to discriminate patients with and without FD (sensitivity: 87%, specificity: 82.8%). A mixed reflux cutoff of 34 episodes/24 hours was identified to discriminate PPI responders from nonresponders (sensitivity: 84.8%, specificity: 69%). At multivariate analysis, an abnormal number of air swallows and of mixed refluxes were significantly associated to FD and PPI refractoriness. CONCLUSION: Our study highlights the relevant role of excessive air swallowing in eliciting both dyspepsia and refractoriness of typical GERD symptoms to PPI therapy.

Protective Role of Natural Compounds under Radiation-Induced Injury.

In recent years, evidence has shown the potential therapeutic effects of different natural compounds for the prevention and treatment of radiotherapy-induced mucositis (RIOM). RIOM represents one of the most frequent side effects associated with anti-neoplastic treatments affecting patients' quality of life and treatment response due to radiation therapy discontinuation. The innate radio-protective ability of natural products obtained from plants is in part due to the numerous antioxidants possessed as a part of their normal secondary metabolic processes. However, oxygen presence is a key point for radiation efficacy on cancer cells. The aim of this review is to describe the most recent evidence on radiation-induced injury and the emerging protective role of natural compounds in preventing and treating this specific damage without compromising treatment efficacy.

Spotlight on the treatment armamentarium of concomitant psoriasis and inflammatory bowel disease: a systematic review.

BACKGROUND: Psoriasis and inflammatory bowel diseases share common immunological pathomechanisms and therefore similar treatment options. OBJECTIVE: To assess already existing therapies and their efficacy versus adverse effects and paradoxical reactions in patients presenting with either disease or both. DATA SOURCES: A systematic search of the PubMed and Science.gov databases was performed for the period 2018-2020. Only articles in English were selected. Search terms included a combination of keywords: adalimumab, infliximab, etanercept, golimumab, certolizumab, ustekinumab, guselkumab, vedolizumab, secukinumab, ixekizumab, brodalumab, acitretin, cyclosporine, methotrexate, apremilast, mycophenolate mofetil, sulfasalazine, hydroxyurea, azathioprine, 6-thioguanine, tacrolimus, leflunomide and fumaric acid esters in combination with each of the following: paradoxical, psoriasis, psoriatic arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis. Other potentially relevant articles were identified by manually checking the references of the included literature. STUDY SELECTION: Recent reviews and meta-analyses, pooled analyses, cohort studies, observational studies, care reports were all included. CONCLUSIONS: Psoriasis and IBD can be treated concurrently as they share common inflammatory pathways. TNF-α inhibitors and IL-12/23 have been successful in treating both psoriasis and IBD. IL-17 inhibitors are recognized treatments for psoriasis but have the potential to exacerbate IBD. Newer molecules require further clinical trials and real-life studies in order to confirm their efficacy and safety.

Reflux characteristics triggering post-reflux swallow-induced peristaltic wave (PSPW) in patients with GERD symptoms.

BACKGROUND: Esophageal chemical clearance has been evaluated with the post-reflux swallow-induced peristaltic wave (PSPW) index. The factors triggering PSPW in Gastro-esophageal reflux disease (GERD) have not yet been investigated. This multicenter study was aimed at evaluating the characteristics of reflux episodes associated with PSPW occurrence in patients with typical GERD symptoms. METHODS: Impedance-pH tracings from patients with typical reflux symptoms were analyzed. Sixteen healthy subjects were included for comparison. Multivariate analysis was performed to determine predictors of PSPW events. KEY RESULTS: Impedance-pH tracings from 60 patients and 16 healthy subjects were evaluated. A total of 3454 refluxes were recorded. In patients, comparing reflux episodes followed with those not followed by a PSPW, significantly higher proportions of acid (79% vs. 74%, p: 0.02), mixed (47% vs. 32%, p: 0.0001) and proximal refluxes (34% vs. 20%, p: 0.0001) were observed. A multivariate analysis, acid (OR: 1.3, 95% CI: 1.05-1.6), mixed (OR: 2, 95% CI: 1.6-2.3), and proximal (OR: 2.1, 95% CI: 1.7-2.5) refluxes were independently associated with PSPWs. Reflux episodes followed by a PSPW were characterized by a significantly higher bolus clearing time [(mean ± SD) 41 s ± 6 s vs. 30 s ± 5 s, p < 0.05] whereas nadir pH value of reflux events preceding PSPWs was tangentially but not significantly lower [(mean ± SD) 2.61 ± 1.22 vs. 2.74 ± 1.26, p: 0.057]. CONCLUSIONS AND INFERENCES: Acid, mixed and proximal refluxes, and their duration are key factors in eliciting PSPWs. PSPW represents a response to reflux directly related to the potential harmfulness of reflux contents.

Early impairment of food intake in patients newly diagnosed with cancer.

Background: Patients with gastrointestinal or lung cancer often suffer from a loss of appetite (anorexia), resulting in reduced food intake (hypophagia) and body weight loss. This study evaluated the prevalence of anorexia, hypophagia, pre-cachexia and cachexia in patients with cancer at time of diagnosis. Patients and methods: Patients with newly diagnosed gastrointestinal or lung cancers were included. Body mass index (BMI) and weight loss over the prior 6 months were recorded. Patients were assessed for (pre-)cachexia and for anorexia using the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) and a specific anorexia questionnaire (AQ). Energy and protein intake were calculated through food diaries. Patients were considered hypophagic if intake was ≤70% of guideline-recommended levels. Results: Overall, 102 patients [53 male; median age: 67 (range, 21-88) years] were enrolled. Mean BMI (± standard deviation) was 23.1 ± 3.4 kg/m2; average percentage of weight loss was 10.1 ± 7.8%. At diagnosis, 68% (69/102) of patients had cachexia, and 11% (11/102) pre-cachexia. Prevalence of anorexia was 57% (58/102) and 75% (76/102) according to FAACT and AQ, respectively. Forty-eight percent (49/102) of patients had hypophagia. Patients with anorexia had lower daily energy (p = 0.002) and protein intake (p = 0.0257), and greater percentage of weight loss (p = 0.0005). In patients with hypophagia, negative correlations were observed between percentage of weight loss and total daily calorie (r = -0.40; p = 0.01) and protein intake (r = -0.340; p = 0.018). Conclusion: Anorexia, inadequate nutritional intake and cachexia are highly prevalent in patients with gastrointestinal or lung cancer at diagnosis. Negative protein and energy balance may play an important role in the pathogenesis of cachexia. Early multimodal strategies to improve food intake are urgently needed.

Gut Microbiota and Related Electronic Multisensorial System Changes in Subjects With Symptomatic Uncomplicated Diverticular Disease Undergoing Rifaximin Therapy.

Background: Intestinal dysbiosis might play a pathogenetic role in subjects with symptomatic uncomplicated diverticular disease (SUDD), but the effect of rifaximin therapy has been scantly explored with regard to gut microbiota variations in patients with SUDD. Aims: To verify to which extent rifaximin treatment affects the gut microbiota and whether an electronic multisensorial assessment of stools and breath has the potential for detecting these changes. Methods: Breath and stool samples were collected from consecutive patients with SUDD before and after a 7 days' therapy with rifaximin. Stool microbiota was assessed, and the electronic multisensorial assessment was carried out by means of the BIONOTE electronic (e-)tongue in stools and (e-)nose in breath. Results: Forty-three subjects (female 60%, median age 66 years) were included, and 20 (47%) reported clinical improvement after rifaximin therapy. Alpha and beta diversity of stool microbiota did not significantly change after treatment, while a significant variation of selected taxa was shown (i.e., Citrobacter, Coprococcus, Anaerotruncus, Blautia, Eggerthella lenta, Dehalobacterium, SMB53, and Haemophilus parainfluenzae). Overall, the electronic multisensorial system suboptimally mirrored microbiota changes, but it was able to efficiently predict patients' clinical improvement after rifaximin with accuracies ranging from 0.81 to 0.98. Conclusions: In patients with SUDD, rifaximin administration is associated with significant variation of selected taxa. While inaccurate in predicting gut microbiota change, an electronic multisensorial system, made up of e-tongue and e-nose, was able to predict clinical improvement, thus potentially qualifying as an easy and cheap tool to forecast subjects taking most likely benefit from rifaximin therapy.

The Results From Up-Front Esophageal Testing Predict Proton Pump Inhibitor Response in Patients With Chronic Cough.

INTRODUCTION: The clinical management of chronic cough patients is challenging, and their response to proton pump inhibitors (PPIs) is considered as unsatisfactory. Few data concerning the association between impedance-pH variables and PPI response in these patients are available. Mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave (PSPW) index increase the diagnostic yield of impedance-pH in gastroesophageal reflux disease. METHODS: Demographic, clinical, and endoscopy findings; impedance-pH; and high-resolution manometry tracings from consecutive patients assessed for cough were evaluated. Univariable and multivariable regression models were generated to evaluate the association between impedance-pH and high-resolution manometry findings, endoscopic and clinical characteristics, and PPI response. RESULTS: A total of 178 patients were included. Eighty-four of 178 cough patients (47.2%) displayed grade C-D erosive esophagitis or were characterized by a pathological acid exposure time (AET) and/or positive symptom association probability/symptom index. When also considering MNBI and PSPW, 135 of 178 patients (75.8%) were characterized by the evidence of reflux disease (P < 0.001). Eighty patients (44.9%) had cough responding to PPIs, whereas 98 (55.1%) were nonresponders (P = 0.071). At the receiver operating characteristic analysis, both PSPW index and MNBI were associated to PPI responsiveness. MNBI and PSPW index showed higher sensitivity in predicting PPI response compared with AET and symptom association probability/symptom index. The area under the curves of MNBI and PSPW index were significantly higher than that of AET (P < 0.01 for both comparisons). When patients were stratified according to AET and excluding those with erosive esophagitis, pathological MNBI or PSPW index, hiatal hernia, and hypomotility features were associated to PPI response in all groups. DISCUSSION: Our results demonstrate the usefulness of an up-front esophageal testing in discriminating reflux-related cough patients and predicting PPI response.